Biomedical subjects

E L Franco

Publications and source records attributed to E L Franco.

At least 19 recordsLinked to original sources

PubMed1992

Measurement errors in epidemiological studies of human papillomavirus and cervical cancer.

Measurement errors have been an important concern in studies of human papillomavirus (HPV) and anogenital cancers. Misclassification of HPV infection status is a possible explanation for incoherent findings in previous epidemiological studies purporting to show an etiological role for HPV in cervical cancer. Even low levels of misclassification of HPV infection can cause severe underestimation of HPV prevalence in field surveys, bias the association between HPV and sexual activity, and impair the ability to control statistically the relation between sexual activity and neoplasia by viral status. The present report focuses on aspects that have not been elaborated in two previous studies (Kaldor, 1989; Franco, 1991). Emphasis is given to effects of measurement errors of HPV infection status in biasing the association with cervical neoplasia under more complex scenarios, e.g., differential misclassification between cases and controls in a case-control study, and non-differential misclassification of both viral infection and cervical neoplasia in cross-sectional cytology surveys and cohort studies. Some simple numeric formulae are given that allow the correction of prevalence rates and epidemiological measures of effect, such as the odds ratio and the relative risk, under the latter conditions of misclassification constraint. These formulae have been used to correct estimates from recent epidemiological studies using hypothetical misclassification scenarios in order to obtain clues on the magnitude of the underlying relationship between HPV and cervical cancer.

Bias↗

PubMed1991

Epidemiological and clinical correlations with genetic characteristics of Wilms' tumor: results of the Brazilian Wilms' Tumor Study Group.

The epidemiological and clinical features of Wilms' tumor (WT) were analyzed in 176 patients admitted to the Brazilian WT Study Group. The occurrence of congenital anomalies (9.1%) and the M:F ratio (0.83) were comparable to those observed by the US National WT Study and the International Society of Pediatric Oncology trials. Bilateral cases were younger on average than unilateral cases (37.2 vs. 45.0 months). Ethnic group and gender were also associated with age, with non-white children being generally older (46.1 months) than whites (39.5 months), and boys being younger than girls (37.0 vs. 46.1 months). However, the most important factor in association with age at diagnosis was disease stage. No early disease patients were diagnosed after 8 years of age (mean: 37.5 months), whereas 10% of those with advanced disease were diagnosed between the ages of 8 and 10 years (mean: 56.3 months). There were no clear distinctions in age distributions on the basis of the presence of tumor multicentricity, intra- or perilobar nephroblastomatosis, and of a combination of putative genetic determinants. The mean age at diagnosis for cases with congenital defects was higher than that for the remaining patients. Some of the study results are in support of the recessive oncogene model for WT. However, the possible confounding effect of disease stage and the strong interdependence of the remaining factors may be masking important relations in regard to mutational events occurring during embryogenesis.

Age Factors↗

PubMed1991

Single-dose versus fractionated-dose dactinomycin in the treatment of Wilms' tumor. Preliminary results of a clinical trial. The Brazilian Wilms' Tumor Study Group.

A clinical trial was conducted by the Brazilian Wilms' Tumor (WT) Study Group to compare the single-dose (60 micrograms/kg x 1 day) administration of dactinomycin (AMD) with the standard fractionated dose (15 micrograms/kg/d x 5 days) used in the US National WT Study. Except for the AMD administration, treatment for all patients followed that of the latter study. Patients were randomized to receive either of the two AMD regimens in the schedules most appropriate for their stage and histologic condition. One hundred seventy-six children with WT entered the study until December 1988. No significant differences in overall or relapse-free survival distributions were observed between treatment arms using data for all patients or data stratified by disease stage. Two-year survival rates were 83.0% and 85.3% for patients receiving the fractionated and single doses of AMD, respectively. Survival distributions could also be compared once patients with protocol violations were excluded. The overall 2-year survival rates were 89.7% and 88.6% and the relapse-free 2-year survival rates were 78.2% and 76.1% for the fractionated and single AMD doses, respectively. Altered liver function was seen in three patients who received fractionated dose and in four patients who received the single AMD dose. Acute toxicity was observed in only one patient of the fractionated-dose group and in zero of the patients of the single-dose group. At the closing date, patients assigned to the simplified AMD regimen had accumulated 1840 days less of hospital stay than those treated by the standard regimen.

Child↗

PubMed1991

Prognostic factors in laryngeal cancer patients submitted to surgical treatment.

The authors studied some demographic, clinical, pathologic, and therapeutic variables in relation to the disease-free interval (DFI) and to the overall survival of laryngeal cancer patients. The patient population consisted of 278 consecutive cases of primary laryngeal cancer who had been admitted to four head and neck surgery services in Sao Paulo and Curitiba (Brazil) between 1973 and 1986. All patients had surgical treatment. Although several variables exhibited individual associations with survival, only a few were deemed to have independent prognostic value using multivariate regression techniques based on Cox's proportional hazards model. The primary tumor stage (T index) represented the variable with the highest predictive strength with respect to survival. Hazard ratios for the risk of disease recurrence were 2.3 (T2-3 vs. T1) and 4.3 (T4 vs. T1). Hazard ratios for the risk of death were 1.6 (T2-3 vs. T1) and 3.3 (T4 vs. T1). The following additional factors were also independently associated with the DFI: age, site of primary tumor (transglottic, glottic, or supraglottic), extracapsular spread of lymph node metastasis, surgical margins, type of paratracheal node dissection, and prior tracheostomy. Except for extracapsular spread, the same factors related to the DFI were also significantly related to the overall survival. Race, sex, N-stage, vascular embolization, and histological grade were other independent predictors of the risk of death.

Aged↗

PubMed1991

Multiple cancers of the upper aero-digestive tract: the challenge of risk factor identification.

Carcinomas of the upper aero-digestive tract (UADT) are among the most common neoplasms, particularly in developing countries. The generally poor prognosis for UADT cancer patients is further complicated by the occurrence during follow-up of additional cancers of the same or related sites. Proper quantification of the incidence of these second cancers and characterization of their risk factors have been plagued with methodological difficulties. The effects of tobacco and alcohol consumption vary with anatomic site, which requires that matching or adjustment by site be performed in any comparisons between single primary and multiple primary patients. Clinical variables, such as disease extension, treatment and survival, also influence risk of second malignancies. However, these parameters are also strongly interrelated, which makes it difficult to characterize their individual associations with risk or to control for their confounding effects when examining other variables. These shortcomings should be taken into consideration in the design of studies searching for genetic and other inter-individual variations in susceptibility to multiple UADT malignancies.

Head and Neck Neoplasms↗

PubMed1991

Risk factors for second cancers of the upper respiratory and digestive systems: a case-control study.

A case-control study of determinants of multiple cancers of the upper respiratory and digestive system (URDS) was conducted using a patient cohort-nested design. We analyzed demographic and risk factor information and clinical variables related to the index cancer for 85 cases of multiple cancers and 170 controls matched on sub-site of the index cancer of the case and date of hospital admission. Follow-up information for the control group was used to infer the person-years-at-risk for the cohort of 1977 patients. URDS cancer patients experienced a 10.7 times (95% confidence interval: 8.5-13.2) higher risk of additional related cancers than the general population. Although controls had cancers of the same sites as those of cases and thus, strongly tobacco and alcohol-related, there were marked residual effects for these two risks factors. In addition, characteristics related to the extension and clinical course of the index cancer were strongly associated with the patient's risk of developing additional cancers.

Adult↗

PubMed1991

The sexually transmitted disease model for cervical cancer: incoherent epidemiologic findings and the role of misclassification of human papillomavirus infection.

The definition of cervical neoplasia as a sexually determined disease caused by some types of human papillomavirus has been widely accepted. Recent epidemiologic studies, however, have failed to identify a correlation between sexual activity and human papillomavirus infection. Moreover, sexual activity has also been shown to be independent of human papillomavirus infection in increasing cervical cancer risk. These incoherences are analyzed with respect to etiologic models for cervical neoplasia and by considering the role of misclassification of human papillomavirus infection in interpreting the relations assumed under these models. Even small levels of misclassification can considerably distort (1) the presumed prevalence of viral infection, (2) the association between sexual activity and human papillomavirus infection, and (3) the ability to control the relation between sexual activity and cancer by human papillomavirus infection. In field surveys, the presumed rates of human papillomavirus infection based on a DNA assay such as the filter in situ hybridization may be a gross overestimation of the true viral prevalence. Use of moderately misclassified human papillomavirus infection test results for effect estimation and covariate adjustment in data analysis may seriously distort the underlying relations. Consequently, considering these conditions, the apparent incoherence of recent epidemiologic findings should not be construed as evidence against the role of human papillomavirus in the etiology of cervical cancer or the validity of the sexually transmitted disease model.

Adolescent↗

PubMed1990

Independent prognostic value of laminin receptor expression in breast cancer survival.

We studied the possible prognostic role of laminin, estrogen (ER), and progesterone (PR) receptors and other pathological factors in relation to the disease-free interval and overall survival of female breast carcinoma patients. Multivariate analyses of clinical and pathological data with respect to the above survival time variables were performed by Cox regression. The statistical dependence of prognosis on ER, PR, and tumor size was based on the discriminant cutoff value that could best distinguish between survival curves. Axillary nodal status was the most significant independent factor in the prediction of both disease-free interval and overall survival of these patients. Use of the information on laminin receptor expression, PR concentration, tumor size, lymphocytic infiltrate, and tumor necrosis improved significantly the prediction of the risk of recurrence. Patients with tumors expressing laminin receptors had 40% less risk of recurrence (P = 0.0209) than those with no expression. On the other hand, four covariates were independently predictive of the risk of death: axillary nodal status, lymphocytic infiltrate, PR and ER concentration. There was a marginally significant (10% level) interaction between tumor size and lymphocytic infiltrate with respect to the prediction of the risk of recurrence. The above sets of variables were used to classify patients into risk groups for the prediction of recurrence and death.

Breast Neoplasms↗

PubMed1990

Microcomputer-assisted multivariate survival data analysis using Cox's proportional hazards regression model.

We describe a microcomputer program (COXSURV) for proportional hazards multiple regression analysis of survival and other failure-time data generated in clinical trials and in retrospective clinical epidemiology studies. COXSURV is menu-driven and has powerful variable factoring and data exploratory capabilities for multivariate modeling. A batch mode allows automatic uni- or multivariate analyses for confounder summarization. Model selection for predictive purposes is possible through a step-up algorithm. The partial likelihood method used in the program allows the use of either discrete or continuous time scales by treating tied uncensored observations by either the exact method or by a robust approximation method. The program calculates most standard model fitting statistics for either overall or stratified analyses and uses data layout files compatible with those of other related epidemiologic analysis software.

Algorithms↗

PubMed1990

Diagnostic performance indices for immunofluorescent tests and enzyme immunoassays of leishmaniasis sera from northern and north-eastern Brazil.

A total of 341 sera were screened for anti-Leishmania IgA, IgG, and IgM antibodies by immunofluorescent (IF) tests and enzyme immunoassay (ELISA). Altogether, 292 of the sera originated from patients with clinically as well as parasitologically diagnosed (positive lesion imprint or the Montenegro skin test) cutaneous leishmaniasis; 49 of the sera were from controls from the same base population. In terms of diagnostic performance, the ELISAs for IgG and IgM yielded indices of diagnostic utility, and the positive predictive value for the IgG-ELISA was 94.6%. A remarkably high specificity (100%) was obtained with the IgA-IF test, but its sensitivity was very low.

Adolescent↗

PubMed1989

Risk factors for oral cancer in Brazil: a case-control study.

A case-control study of risk factors for carcinomas of the tongue, gum, floor, and other specified parts of the mouth was conducted in 3 metropolitan areas in Brazil: São Paulo (southeast), Curitiba (south), and Goiânia (central-west). We analyzed information on demographics, occupational history, environmental exposures, tobacco smoking and alcohol drinking habits, as well as diet, oral and other health characteristics obtained from interviews with 232 cases and 464 hospital non-cancer controls matched for 5-year age-group, sex, hospital catchment area and trimester of admission. Tobacco and alcohol consumption were the strongest risk factors irrespective of the anatomical site. The adjusted relative risks (RR) for ever vs. never smokers were: 6.3, 13.9, and 7.0, for industrial-brand cigarettes, pipe, and hand-rolled cigarettes, respectively. A strong correlation was seen between number of pack-years and risk. The RR for the heaviest vs. the lowest consumption categories (greater than 100 vs. less than 1 pack-years) was 14.8. Risk levels generally decreased to those of never smokers after 10 years had elapsed since stopping smoking. The risk associated with alcohol was mostly evident for wine (cancer of the tongue) and "cachaça" (all sites), a hard liquor distilled from sugar cane. Other important risk factors were drinking "chimarrão" (a type of maté), use of a wood stove for cooking, and frequent consumption of charcoal-grilled meat and manioc. Oral hygiene characteristics represented correlates of disease risk. A significant protective effect was observed for consumption of carotene-rich vegetables and citric fruits, but not for green vegetables in general.

Age Factors↗

PubMed1989

Epidemiologic correlates of cervical neoplasia and risk of human papillomavirus infection in asymptomatic women in Brazil.

To investigate whether the epidemiologic correlates of cervical cancer are predictors of infection with genital human papillomavirus (HPV), we performed a prevalence survey in two metropolitan areas of Brazil, Recife and São Paulo. The data records of four randomly selected HPV-negative women were matched on the basis of age, clinic, and admission period with those of each of 136 patients with positive HPV DNA hybridizations. Anal intercourse [prevalence rate ratio (PRR) = 1.7] and current pregnancy (PRR = 2.3) were the only variables associated with HPV 6/11 infection (P less than .10). Only the frequency of gynecologic consultations was associated (negatively) with risk of HPV 16/18 infection (P = .0175). Our data failed to provide evidence for the existence of shared risk factors for genital HPV infection and cervical cancer. The frequency of mixed HPV infections was 13 times higher than expected, a finding suggestive of the existence of additional determinants of HPV infection not akin to the general behavioral characteristics of women that are probed in the study.

Adult↗

PubMed1989

Tumor and serum beta-2-microglobulin expression in women with breast cancer.

To investigate whether the tumor expression of beta-2-microglobulin (beta 2-M) could serve as a marker of tumor biologic behavior, the authors studied specimens of breast carcinomas from 60 consecutive female patients. Presence of beta 2-M was analyzed by immunohistochemistry. No significant correlations were found between tumor beta 2-M expression and several histologic attributes such as type, histologic and nuclear grades, mitotic index, necrosis, vascular invasion, and lymphocytic infiltration. Likewise, beta 2-M was not associated with markers of disease extension such as TNM, (UICC, classification of malignant tumors) staging and axillary lymph node involvement or with estrogen, progesterone, and glucocorticoid receptor levels. However, there was a significantly positive association between tumor beta 2-M expression and the degree of lymphocytic infiltration in the tumor tissue. Beta 2-M serum levels were determined by an enzyme-linked immunosorbent assay in samples from 22 of the above women. Although some of the highest values had been obtained in women with larger (T4) primary tumors, the authors failed to detect any statistical relationship between beta 2-M expression in the tumor with serum levels or between serum beta 2-M and the above histologic, laboratory, and clinical factors.

Adult↗

PubMed1989

Epidemiologic programs for computers and calculators. A microcomputer program for multiple logistic regression by unconditional and conditional maximum likelihood methods.

A frequent procedure in matched case-control studies is to report results from the multivariate unmatched analyses if they do not differ substantially from the ones obtained after conditioning on the matching variables. Although conceptually simple, this rule requires that an extensive series of logistic regression models be evaluated by both the conditional and unconditional maximum likelihood methods. Most computer programs for logistic regression employ only one maximum likelihood method, which requires that the analyses be performed in separate steps. This paper describes a Pascal microcomputer (IBM PC) program that performs multiple logistic regression by both maximum likelihood estimation methods, which obviates the need for switching between programs to obtain relative risk estimates from both matched and unmatched analyses. The program calculates most standard statistics and allows factoring of categorical or continuous variables by two distinct methods of contrast. A built-in, descriptive statistics option allows the user to inspect the distribution of cases and controls across categories of any given variable.

Algorithms↗

PubMed1989

Age and lateness of referral as determinants of extra-ocular retinoblastoma.

The risk of extra-ocular (EO) vs. intra-ocular disease was evaluated in a retrospective study of 158 consecutive cases of retinoblastoma (age range: birth to 113 months) admitted to the A.C. Camargo Hospital, Brazil, between January 1975 and December 1985. The risk of having EO disease was strongly dependent on the age at diagnosis and lateness of referral. The older the child at first admission the higher the risk of finding EO disease at diagnosis. This association was considerably more pronounced among sporadic unilateral cases. Patients with a history of longer duration of symptoms were more likely to exhibit EO disease than patients seeking medical attention within six months of the onset of the disease. This association seemed to be confounded by the genetic form of the disease as the increase in risk of EO disease appeared later among the germinal cases. Clinical stage and lateness of referral were the variables most associated with the survival experience of patients.

Age Factors↗

PubMed1989

Evaluation of serological diagnostic indices for mucocutaneous leishmaniasis: immunofluorescence tests and enzyme-linked immunoassays for IgG, IgM and IgA antibodies.

The sensitivity, specificity, positive predictive value, negative predictive value, and efficiency of immunofluorescence (IF) and enzyme-linked immunoassays (ELISA) for IgG, IgM and IgA antibodies were assessed on sera from mucocutaneous leishmaniasis patients and controls. The sensitivity of the IgG-ELISA test was 93.3% with 95% confidence interval higher than what could be due to a random test not associated with the disease. The specificity of all tests, except the IgM-ELISA, gave indices that could not have been due to chance. The IgG-ELISA and IgG-IF had the highest positive predictive value and the kappa statistic showed that the strength of agreement between the disease and the test was strongest for IgG-ELISA. The IgG-ELISA had a negative predictive value with 95% confidence limits that were not due to chance alone. Efficiency was highest for IgG-ELISA and IgG-IF. These results were obtained using sera from patients with severe or long-standing disease and from controls in whom the disease was ruled out by a negative Montenegro skin test. In field surveys where the differences between cases and controls are less easy to define the diagnostic indices of these tests may vary with the disease prevalence.

Adolescent↗

PubMed1988

Factors of prognostic importance in childhood non-Hodgkin's lymphoma treated with two modified LSA2-L2 protocols. A multivariate analysis approach.

The results of therapy given to 74 children with advanced disease, abdominal non-Hodgkin's lymphoma were retrospectively evaluated with respect to the major prognostic factors related to disease outcome. The first 36 patients admitted in the study were treated with a modified LSA2-L2 protocol, and the remaining patients received the same regimen with the addition of intermediate-dose methotrexate (MTX) intravenously during the induction phase (LSA2-L2-MTX). The last ten patients admitted were given a leucovorin rescue along with the administration of MTX. The relative efficacy of the LSA2-L2-MTX over the baseline LSA2-L2 regimen was analyzed by multivariate statistical methods taking into consideration several candidate coprognostic factors. The risk of treatment failure was substantially reduced (55%) with the use of the LSA2-L2-MTX regimen. Rescue with leucovorin did not contribute a further significant gain in treatment efficacy, although fewer toxicity-related problems were observed as compared to the no-rescue period. Five prognostic factors emerged as significantly explanatory of the risk of treatment failure in addition to protocol type: lymphocyte count, disease stage, surgical debulking, sex, and nutritional status. Based on these variables, a logistic regression equation could be derived to identify groups that were at risk for treatment failure.

Abdominal Neoplasms↗

PubMed1988

Plasminogen activator expression and steroid hormone receptors in female breast cancer: a multifactorial study.

In order to evaluate the relationship of plasminogen activator (PA) activity to the expression of estrogen (ER) and progesterone (PR) receptors, we assayed primary tumor specimens from 121 cases of female breast cancer. Other clinical and histopathological variables were also investigated with respect to their possible association with PA activity in the samples. Statistical correlations were examined by stratified analysis techniques and by multiple regression methods. PA activity was higher in tumors which were ER+PR+ than in those exhibiting other subsets of joint receptor expression, a finding which was particularly predominant in tumors from post-menopausal women. Of the other variables examined, only disease stage, nodal status and vascular infiltration presented marginal positive statistical associations with PA activity, although this was not confirmed by multivariate analysis. The latter technique showed that the presence of PR was sufficient to explain the variation in PA levels. However, ER emerged as the sole significantly explanatory factor when ER+PR- patients were removed from analysis. Both PR and age (negatively) were independent contributory factors for PA activity in the analysis of post-menopausal women. None of the variables examined emerged as being significantly associated with PA when data from pre-menopausal patients were used. These findings indicate that PA activity in breast tumor samples is statistically associated with the expression of functional estradiol receptors, although to a lesser extent than PR.

Adult↗